Disease relevance of B2R

• We report that incubation of pig iris sphincter with lipopolysaccharide from Escherichia coli caused a marked and time-related up-regulation of B1, accompanied by a reduction of B2 receptor-mediated contractile responses [1].

High impact information on B2R

• This potentiation was prevented by serine protease inhibitors and was antagonized by B2-receptor blockade [2].
• The increase in RL induced by cold air after L-NAME was abolished by the tachykinin NK2-receptor antagonist SR 48968 or the kinin B2-receptor antagonist, HOE 140 [3].
• With the new tracer as label, the B2 receptor antagonists D-Arg0-[Hyp3,Thi5,D-Tic7,Oic8]BK and D-Arg0-[Hyp3,Thi5,8,D-Phe7]BK recognized both binding sites with very high affinity in guinea pig ileum membranes, classifying these sites as B2 receptors [4].
• In the central airways, the contribution of sensory neuropeptides to the bradykinin response is greater than that caused by direct stimulation of the B2 receptor on the endothelium at the postcapillary venule of the bronchial circulation [5].
• D-Arg[Hyp3,D-Phe7]-Bk (NPC567) and D-arg[Hyp3,Thi5,8,D-Phe7]-Bk (NPC349), B2 receptor antagonists, were weak inhibitors of Bk-induced bronchoconstriction in vivo and were virtually inactive as antagonists of Bk-induced airway smooth muscle contraction [6].

Biological context of B2R

• In animals receiving the selective B2 receptor antagonist Hoe-140 a significant attenuation of the peak fall in blood pressure to DXS was observed [7].
• Two potent B2 receptor antagonists, FR173657 (1 and 100 nM) and icatibant (10 nM), significantly antagonized the inhibitory action of serosally applied bradykinin on peristalsis (P<0.01), whilst the B1 receptor antagonist, Lys-[des-Arg9, Leu8]-bradykinin (100 nM) was inactive (P>0.05) [8].
• ACE inhibitor and AT1 antagonist blockade of deformation-induced gene expression in the rabbit jugular vein through B2 receptor activation [9].
• In the presence of B2 receptor antagonist, icatibant (100 nM), Ach-induced vasodilation was unaffected, while Bk-induced vasodilaton was abolished before and after XOX [10].

Anatomical context of B2R

• Thus, in the presence of bradykinin, Ang 1-7 relaxes pig coronary arteries via a PD-123319-sensitive mechanism involving nitric oxide, kinins and the BK B2 receptor [11].
• MEN16132, a novel potent and selective nonpeptide kinin B2 receptor antagonist: in vivo activity on bradykinin-induced bronchoconstriction and nasal mucosa microvascular leakage in anesthetized guinea pigs [12].
• D-Arg[Hyp3,Igl5,D-Igl7,Oic8]BK (code name B 9430), a non-selective bradykinin B1/B2 receptor antagonist, also administered intraperitoneally (1 mg kg(-1)), decreased eosinophil and macrophage counts by 62% and 80% in bronchoalveolar fluid [13].
• These results indicate that the specific [125I-Tyr8]-BK binding sites present in the guinea pig spinal cord belong to the B2 receptor subtype [14].
• CONCLUSIONS: The BK B2 receptor antagonist NPC-567 seems to be effective in inhibiting the acute response to allergen in the pig airways, possibly due to inhibition of mast cell activation via indirect mechanisms [15].

Associations of B2R with chemical compounds

• Both contraction and relaxation by bradykinin were blocked by the kinin B2 receptor antagonist, HOE 140 [16].
• We also studied the effects of a B1 receptor agonist and antagonist, a B2 receptor antagonist, and the cyclooxygenase inhibitor indomethacin [17].
• NPC 567 (DArg[Hyp3,DPhe7]-bradykinin), a B2 receptor antagonist, had no effect on bradykinin-induced 45Ca2+ efflux, but abolished prostaglandin synthesis [17].
• The A(1-7)-induced relaxation was not affected by AT1 or AT2 receptor blockade or cyclo-oxygenase inhibition, but was attenuated by the B2 receptor antagonist, Hoe 140, and augmented by the angiotensin-converting enzyme (ACE) inhibitor, quinaprilat [18].
• The pressor response to IP BK was reduced by concomitant IP injection of lidocaine or of D-Arg[Hyp3,D-Phe7,Leu8]BK, a B2 receptor antagonist [19].

Analytical, diagnostic and therapeutic context of B2R

• This suggests that in this animal model the B1 receptor does not serve the same purpose as the B2 receptor, and that up-regulation of B1 receptors during LPS shock may be an important mechanism of host defence [20].
• METHODS AND RESULTS: Localization of the B2 kinin receptor in membranes prepared from native porcine aortic endothelial cells was evaluated by means of specific [3H]bradykinin binding and immunoprecipitation of the B2 receptor from isolated membranes [21].

References